MTRFR

mitochondrial translation release factor in rescue, the group of Mitochondrial translation release factor family

Basic information

Region (hg38): 12:123233385-123258079

Previous symbols: [ "C12orf65" ]

Links

ENSG00000130921 ∙ NCBI:91574 ∙ OMIM:613541 ∙ HGNC:26784 ∙ Uniprot:Q9H3J6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• combined oxidative phosphorylation defect type 7 (Definitive), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR
• combined oxidative phosphorylation defect type 7 (Moderate), mode of inheritance: AR
• combined oxidative phosphorylation defect type 7 (Strong), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined oxidative phosphorylation deficiency 7; Spastic paraplegia 55, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	3479531; 20598281; 23188110; 24198383

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MTRFR gene.

• Combined_oxidative_phosphorylation_defect_type_7 (105 variants)
• Spastic_paraplegia (97 variants)
• not_provided (36 variants)
• Hereditary_spastic_paraplegia (10 variants)
• Hereditary_spastic_paraplegia_55 (10 variants)
• MTRFR-related_disorder (7 variants)
• not_specified (6 variants)
• Neurodevelopmental_disorder (1 variants)
• Hereditary_motor_and_sensory_neuropathy_with_optic_atrophy (1 variants)
• Epileptic_encephalopathy (1 variants)
• Optic_atrophy (1 variants)
• Abnormal_brain_morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MTRFR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000152269.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				34		34
missense		1	56	2		59
nonsense	2	2				4
start loss						0
frameshift	10	5	3			18
splice donor/acceptor (+/-2bp)	1	1				2
Total	13	9	59	36	0

Highest pathogenic variant AF is 0.000217447

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MTRFR	protein_coding	protein_coding	ENST00000253233	2	25044

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.209	0.754	125657	0	91	125748	0.000362

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.433	102	90.4	1.13	0.00000531	1063
Missense in Polyphen		28	30.652	0.91349		355
Synonymous	1.13	30	38.9	0.770	0.00000256	330
Loss of Function	1.74	2	6.94	0.288	4.80e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00111	0.00111
European (Non-Finnish)	0.000537	0.000536
Middle Eastern	0.000109	0.000109
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May act as a codon-independent translation release factor that has lost all stop codon specificity and directs the termination of translation in mitochondrion. May help rescuing stalled mitoribosomes during translation (By similarity). {ECO:0000250}.
• Disease: DISEASE: Combined oxidative phosphorylation deficiency 7 (COXPD7) [MIM:613559]: A mitochondrial disease resulting in encephalomyopathy. Clinical manifestations include psychomotor delay and regression, ataxia, optic atrophy, nystagmus and muscle atrophy and weakness. {ECO:0000269|PubMed:20598281}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spastic paraplegia 55, autosomal recessive (SPG55) [MIM:615035]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. {ECO:0000269|PubMed:23188110}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0748

Intolerance Scores

• loftool: 0.863
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63

Haploinsufficiency Scores

• pHI: 0.0565
• hipred: N
• hipred_score: 0.267
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: 2810006K23Rik

Gene ontology

• Biological process: translational termination
• Cellular component: mitochondrion;mitochondrial large ribosomal subunit
• Molecular function: translation release factor activity